Natural Product: NPC604569

Natural Product IDNPC604569
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UJEJKGCTUWVBRI-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL73016
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey UJEJKGCTUWVBRI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-15-8-14-16(18(24-3)17(15)23-2)12(21)7-13(25-14)9-4-5-10(19)11(20)6-9/h4-8,19-20H,1-3H3
SMILES COc1cc2oc(-c3ccc(O)c(O)c3)cc(=O)c2c(OC)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   1.927
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.08
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.757
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   98.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.392 Fsp3:   0.167
MCE-18:   19.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.236 Fluc inhibitor:   0.377
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.945
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.717
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.341 Promiscuous compounds:   0.486

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.106 MDCK Permeability:   -4.747
Pgp-inhibitor:   0.136 Pgp-substrate:   0.023
PAMPA:   0.113
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.059
20% Bioavailability (F20%):   0.868 30% Bioavailability (F30%):   0.885
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.972
Plasma Protein Binding (PPB):   92.786% Volume Distribution (VD):   -0.381
Fu: 7.36%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.971
BSEP inhibitor:   0.884

ADMET: Metabolism

CYP1A2-inhibitor:   0.099 CYP1A2-substrate:   0.073
CYP2C19-inhibitor:   0.127 CYP2C19-substrate:   0.153
CYP2C9-inhibitor:   0.219 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.862 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.032 CYP3A4-substrate:   0.706
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.94
HLM stability:   0.636
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  11.374 Half-life (T1/2):  1.544

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.602
Human Hepatotoxicity (H-HT):  0.363 Drug-induced Liver Injury (DILI):  0.79
AMES Toxicity:  0.473 Rat Oral Acute Toxicity:  0.419
Maximum Recommended Daily Dose:  0.62 Skin Sensitization:  0.904
Carcinogencity:  0.698 Eye Corrosion:  0.53
Eye Irritation:  0.986 Respiratory Toxicity:  0.61
Drug-induced Neurotoxicity:  0.095 Ototoxicity:  0.27
Hematotoxicity:  0.138 Drug-induced Nephrotoxicity:  0.046
Genotoxicity:  0.693 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.471 Hek293 Cytotoxicity:  0.407
BCF:   1.356
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.703
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.995
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.334
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO40516 Arrabidaea brachypoda Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[32902988]
NPO40516 Arrabidaea brachypoda Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT183 Individual protein Arachidonate 5-lipoxygenase Rattus norvegicus IC50 = 240.0 nM PMID[3783588]
NPT68 Individual protein Aldose reductase Rattus norvegicus IC50 = 91.2 nM PMID[18585047]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC604569 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7778 Intermediate Similarity NPC608258
0.7636 Intermediate Similarity NPC606105
0.7115 Intermediate Similarity NPC106461
0.7037 Intermediate Similarity NPC138360
0.6981 Remote Similarity NPC14958
0.6923 Remote Similarity NPC302408
0.6786 Remote Similarity NPC25270
0.6727 Remote Similarity NPC215932
0.6491 Remote Similarity NPC605047
0.6316 Remote Similarity NPC100887
0.6207 Remote Similarity NPC108406
0.6207 Remote Similarity NPC162313
0.6071 Remote Similarity NPC600022
0.5833 Remote Similarity NPC292460
0.569 Remote Similarity NPC226973
0.5667 Remote Similarity NPC201136
0.56 Remote Similarity NPC12461
0.55 Remote Similarity NPC120163
0.55 Remote Similarity NPC188203
0.5484 Remote Similarity NPC75215
0.5455 Remote Similarity NPC476283
0.541 Remote Similarity NPC50715
0.541 Remote Similarity NPC18772
0.5333 Remote Similarity NPC47815
0.5333 Remote Similarity NPC609062
0.5323 Remote Similarity NPC167815
0.5323 Remote Similarity NPC20830
0.5312 Remote Similarity NPC258331
0.5263 Remote Similarity NPC118726
0.5254 Remote Similarity NPC29536
0.5246 Remote Similarity NPC22519
0.5246 Remote Similarity NPC610660
0.5238 Remote Similarity NPC160951
0.5172 Remote Similarity NPC70136
0.5172 Remote Similarity NPC275772
0.5167 Remote Similarity NPC75279
0.5161 Remote Similarity NPC78913
0.5156 Remote Similarity NPC47781
0.5085 Remote Similarity NPC101294
0.5085 Remote Similarity NPC278556
0.5085 Remote Similarity NPC69752
0.5085 Remote Similarity NPC279121
0.5082 Remote Similarity NPC241498
0.5082 Remote Similarity NPC239128
0.5067 Remote Similarity NPC45638

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC604569 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.5085 Remote Similarity NPD1511 Phase 2

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data